CLINICAL TRIAL: TREATMENT OF SLEEP PROBLEMS IN CHILDREN WITH AUTISM SPECTRUM DIS

临床试验：自闭症谱系障碍儿童睡眠问题的治疗

• 批准号: 8166701
• 负责人: BOBBI HOPKINS
• 金额: $ 0.88万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166701
• 关键词: Address; Affect; Aftercare; Age; Autistic Disorder; Behavior; Behavioral; Child; Circadian Rhythms; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diagnostic tests; Disease; Dose; Double-Blind Method; Effectiveness; Evaluation; Exposure to; Family; Functional disorder; Funding; Future; Gastroesophageal reflux disease; Goals; Grant; Hormones; Hour; Individual; Institution; Intervention; Life; Matched Group; Measures; Medical; Melatonin; Oral; Outcome Measure; Parents; Participant; Pharmaceutical Preparations; Phase; Placebos; Play; Production; Quality of life; Questionnaires; Recruitment Activity; Research; Research Personnel; Research Project Grants; Resources; Role; Salivary; Sampling; Severities; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep disturbances; Sleeplessness; Source; Structure; Symptoms; Testing; United States National Institutes of Health; Urine; actigraphy; autism spectrum disorder; experience; hypnotic; improved; primary outcome; randomized trial; response; treatment trial

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to examine whether sleep problems in children with autism spectrum disorder (ASD) are related to alterations in the secretion of melatonin (MT), a hormone that plays an important role in regulating the circadian cycle and sleep. Furthermore, we will examine the efficacy of MT for improving sleep in children with ASD. Children with ASD experience high rates of sleep disturbances that potentially contribute to the severity of their cognitive and behavioral dysfunction and to poor quality of life for themselves and their families. It is unclear if irregularities in MT rhythm underlie sleep problems in children with ASD. Their sleep problems are characterized by sleep-wake rhythm abnormalities and symptoms of insomnia including difficulty initiating and maintaining sleep. MT is frequently used to treat these sleep problems; however, its effectiveness as a hypnotic to treat insomnia in children with ASD has not been clearly established. All subjects will be recruited from the Autism Treatment Network after completing rigorous diagnostic testing. Exclusionary criteria include exposure to melatonin in the month prior to the study, current psychoactive medications or medications known to suppress MT secretion, other sleep disorders, such as sleep apnea, and medical disorders that may affect sleep, such as gastroesophageal reflux disease (GERD). Participants¿?? parents will complete a validated sleep questionnaire, which will define the presence or absence of sleep problems. MT onset will be determined by measuring salivary MT levels before and after usual bedtime in ASD children with sleep problems and in a matched group of children with ASD and no sleep problems. Total 24 hour MT production will be determined from urine samples in these same two groups. A double-blind, randomized trial of three oral doses of MT (3, 6, 9 mg) and placebo in children (ages 4-9 years) with ASD and sleep problems will follow a baseline sleep and behavior evaluation. The primary outcome measure will be change in sleep latency as determined by actigraphy at baseline and at the end of the fifth week of each of the treatment trials. Another primary outcome measure will be change in validated behavioral questions given at baseline and during the fifth week of each of the treatment trials. Results from this study will provide a rationale for the development of future trials of circadian rhythm interventions and clinical parameters for the use of MT to manage sleep problems in ASD. Our hypotheses concerning MT are: 1. Children with ASD and sleep problems will have a delay in MT onset and/or have decreased MT secretion over 24 hours; 2. Oral MT will be associated with improvement in sleep and behavior in children with ASD and sleep problems. This is a proposal to study the relationship between melatonin (MT) and sleep problems in children with autism spectrum disorder (ASD), as part of the collaborative research structure of the Autism Treatment Network (ATN). A major goal of the ATN is to conduct clinical research that will have a significant impact on the daily lives and functioning of individuals with ASD and to address immediate concerns of parents. Children with ASD experience high rates of sleep disturbance, which likely contribute to the severity of their daytime cognitive and behavioral dysfunction and to poorer quality of life for them and their families.1, 2 As a step toward addressing sleep problems in ASD, we propose to test two hypotheses. Our first hypothesis proposes that children with ASD and sleep problems will have a delay in MT onset and/or have decreased MT secretion over 24 hours. Our second hypothesis proposes that administration of exogenous MT will result in a decrease in sleep problems and a subsequent improvement in daytime behaviors, with higher doses showing greater effect. This research project has the following specific aims: Specific Aim 1: Characterize the endogenous MT profiles in children with ASD with and without sleep problems. Specific Aim 2: Determine the efficacy of MT used as a hypnotic for improving sleep directly and secondarily improving daytime behavior in children with ASD and sleep problems. We predict that results from this study will reveal lower levels of metabolized MT in children with ASD and sleep problems when compared to ASD children without sleep problems. In addition, we anticipate that children with ASD and sleep problems will have delayed MT onset or altered circadian phase. We predict that participants will experience improved sleep after treatment with oral MT, as indicated by shortened sleep latency. We anticipate that children with altered circadian phase will show better response to treatment with MT. We predict that participants who experience improved sleep will demonstrate improved daytime behaviors as a result of their improved sleep. Data from this study will provide important information concerning circadian rhythm dysregulation in ASD and will support the development of future studies using MT to modify and correct abnormal circadian rhythms.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 我们建议检查自闭症谱系障碍儿童（ASD）的睡眠问题是否与褪黑激素（MT）的分泌变化有关，这是一匹在调查昼夜节律周期和睡眠中起重要作用的马。此外，我们将研究MT改善ASD儿童睡眠的有效性。 ASD患有高度睡眠障碍的儿童有可能导致其认知和行为功能障碍的严重性以及对自己和家人的生活质量差。目前尚不清楚ASD儿童的睡眠问题是MT节奏的违规行为。他们的睡眠问题的特征是睡眠节奏异常和失眠症状，包括难以发起和维持睡眠。 MT经常用于治疗这些睡眠问题；但是，在完成严格的诊断测试后，将从自闭症治疗网络中招募其作为ASD儿童失眠的催眠症的有效性。排他性标准包括在研究前一个月暴露于褪黑激素，当前的精神活性药物或已知可以抑制MT分泌的药物，其他睡眠障碍，例如睡眠呼吸暂停以及可能影响睡眠的医学疾病，例如胃食管治疗疾病（GERD）。参与者?? ??父母将完成经过验证的睡眠问卷，这将定义睡眠问题的存在或不存在。 MT发作将通过在患有睡眠问题的ASD儿童以及与ASD且无睡眠问题的匹配的儿童组中测量通常睡前和之后的唾液MT水平来确定。总共24小时的MT产生将从这两组中的尿液样品中确定。三种口服剂量的MT（3、6、9毫克）和安慰剂的双盲，随机试验（4-9岁）的ASD和睡眠问题将遵循基线睡眠和行为评估。根据基线时和每个治疗试验的第五周结束时，由行为摄影确定的睡眠潜伏期中的主要结局指标将改变。在基线和每个治疗试验的第五周给出的经过验证的行为问题中，将改变另一个主要的结果指标。这项研究的结果将为开发未来的昼夜节律干预措施和临床参数的试验提供基本原理，用于使用MT来管理ASD中的睡眠问题。 我们关于MT的假设是：1。患有ASD和睡眠问题的儿童将在MT发作和/或在24小时内延迟MT分泌； 2。口服MT将与ASD和睡眠问题儿童的睡眠和行为改善有关。 这是研究自闭症治疗网络（ATN）协作研究结构的一部分，研究自闭症谱系障碍（ASD）儿童（ASD）儿童的褪黑激素（MT）与睡眠问题之间的关系。 ATN的主要目标是进行临床研究，该研究将对ASD患者的日常生活和功能产生重大影响，并解决父母的直接关注。患有ASD的儿童的睡眠障碍率很高，这可能导致他们白天的认知和行为功能障碍的严重程度以及对他们及其家人的生活质量较差。1，2 作为解决ASD睡眠问题的一步，我们建议检验两个假设。我们的第一个假设提出的提议说，ASD和睡眠问题儿童将在24小时内延迟MT发作和/或MT分泌减少。我们的第二个假设提出的提议是，外源MT的给药将导致睡眠问题减少和随后的白天行为改善，而较高剂量显示出更大的作用。 该研究项目具有以下具体目标： 具体目标1：表征患有和没有睡眠问题的ASD儿童的内源MT谱。 具体目标2：确定MT用作催眠的效率，可直接改善睡眠，其次改善ASD和睡眠问题儿童的白天行为。 我们预测，与没有睡眠问题的ASD儿童相比，这项研究的结果将揭示患有ASD和睡眠问题的儿童的代谢MT水平较低。此外，我们预计患有ASD和睡眠问题的儿童将延迟MT发作或改变昼夜节律。我们预测，通过口服MT治疗后，参与者的睡眠会改善，如睡眠潜伏期所表明的那样。我们预计昼夜节律改变的儿童将对MT的治疗显示更好的反应。我们预测，经历改善睡眠的参与者将由于睡眠的改善而表现出改善的白天行为。 这项研究的数据将提供有关ASD中昼夜节律失调的重要信息，并将支持使用MT修改和纠正异常昼夜节律的未来研究的发展。